1. Field of the Invention
This invention is directed to polymers for use with medical articles and, more specifically, polymers containing novel polyesters.
2. Description of the State of the Art
A current paradigm in biomaterials research is the use of bioabsorbable materials in medical implants. Bioabsorbable materials can be used, for example, as a reservoir for agents that can be therapeutic, prophylactic, diagnostic, or otherwise biologically beneficial. Such agents can be blended, mixed, connected or otherwise combined with the bioabsorbable material. In one example, a bioabsorbable material can serve as a reservoir for agents that create a non-fouling surface, which is a surface that does not become fouled or becomes less fouled with a layer of partially denatured proteins. Uncontrolled protein adsorption on an implant surface is a problem with currently available biomaterial implants and leads to such fouling on the implant surface that can also lead to disease, such as thrombosis, inflammation, a proliferative tissue response, or any combination of these diseases. A mechanism for the creation of diseases due to fouling may include, for example, providing cell-binding sites from adsorbed plasma proteins such as fibrinogen and immunoglobulin G. Platelets and inflammatory cells such as, for example, monocytes, macrophages and neutrophils adhere to the cell-binding sites. A wide variety of proinflammatory and proliferative factors may be secreted and result in disease.
Bioabsorbable materials can also be used to medicate implants by facilitating local administration of a therapeutic or prophylactic substance at a diseased site. A stent is an example of an implant that can be improved with a coating that can serve as a reservoir for the local administration of agents. As a mechanical intervention, stents can physically hold open and, if desired, expand a passageway within a mammal. Typically, a stent may be compressed, inserted into a lumen through a catheter, and then expanded to a larger diameter once placed in a proper location. Examples of patents disclosing stents include U.S. Pat. Nos. 4,733,665, 4,800,882 and 4,886,062.
Stents play an important role in a variety of medical procedures such as, for example, percutaneous transluminal coronary angioplasty (PTCA), which is a procedure used to treat heart disease. In PTCA, a balloon catheter is inserted through a brachial or femoral artery, positioned across a coronary artery occlusion, inflated to compress atherosclerotic plaque and open the lumen of the coronary artery, deflated and withdrawn. Problems with PTCA include formation of intimal flaps or torn arterial linings, both of which can create another occlusion in the lumen of the coronary artery. Moreover, thrombosis and restenosis may occur several months after the procedure and create a need for additional angioplasty or a surgical by-pass operation. Stents are generally implanted to reduce occlusions, inhibit thrombosis and restenosis, and maintain patency within the lumen of the coronary artery.
Local delivery of agents is often preferred over systemic delivery of agents, particularly where high systemic doses are necessary to achieve an effect at a particular site within a mammal, because high systemic doses of agent can often create adverse effects within the mammal. One proposed method of local delivery includes coating the surface of a medical article with a polymeric carrier that can be used as a reservoir for the delivery of agents. There are a large number of biodegradable polymers that have potential for such a use, and a polymer that is useful must be biocompatible, for example, in a vascular environment. The polymer must not elicit an adverse biological response greater than that elicited by stainless steel at all times until the polymer is absorbed. The biological response of a polymer is a complex function of polymer dose, degradation rate, acid generation, monomer compatibility, and response to morphological changes.
Bioabsorbable polymers can be categorized according to the type of labile linkage in the backbone of the polymer such as, for example, polyanhydrides, polyethers, polyesters, and the like. Currently used bioabsorbable polymers include poly(lactide), poly(glycolide), poly(lactide-co-glycolide) and poly(caprolactone), each of which are polyesters that are limited in their applications. For example, those of skill in the art know that poly(L-lactide) is quite strong but is inelastic, has a relatively high acid generation, and can present some biological response problems; and, poly(caprolactone) has a lower acid generation but is quite weak. Each of these polyesters undergo bulk erosion, which is less desirable for a coating material that is used to control release of agents.
Another problem involves regulatory concerns that may arise when agents attached to a polymeric coating remain attached to molecules from the polymeric coating upon degradation of the coating. Since these additional molecules were not considered in the original regulatory approval of the agent, there may be regulatory concerns over possible changes in the agent's biological activity.
Accordingly, there is a need for bioabsorbable polyesters that (i) have improved mechanical and biological response properties for applications that can benefit from such biodegradable polymers, and (ii) can release agents that are substantially free of additional molecules derived from a polymeric coating.